Many medical diagnostic techniques project radiant energy into the body of an animal for testing for the existence of a biomedical disorder or condition. For example, the integrity of the skeletal structure may be examined by passing X-rays through the body. The dense bony material substantially blocks the passage of the X-rays, permitting a doctor or other medical care provider to visually inspect for fractures or other defects in the skeletal structure.
To examine the soft tissue of the body, other techniques are available. These include, among others, CAT scans and magnetic resonance imaging. Both project radiant energy onto the body for obtaining information about the physical structure of the body.
Further, measurement of the level of certain chemicals or compositions within the body is a diagnostic test of particular interest. Radiant energy may be used in these applications as passage of the radiant energy through particular chemicals or compositions often alters the radiant energy in a manner that can be measured and analyzed. For example, the monitoring of the glucose level of the blood is of particular importance to diabetics.
One method of measuring the person's glucose involves projecting polarized radiation onto the body and measuring the optical rotation of the radiation that passes through the body. This optical rotation corresponds to the concentration of the glucose within the body. However, to be effective in measuring the concentration of a component the radiation must be passed through a relatively thin area of the body.
In another example, Larin et al. (Diabetes Care, Vol 25, No. 12, p. 2263-2267) describes a method of the noninvasive blood glucose measurement with optical coherence tomography. The glucose concentration was determined by the slope of the OCT signals. A calibration curve, however, is needed for the glucose concentration.
U.S. Pat. No. 6,403,944, the disclosure of which is incorporated herein by reference, uses a photoacoustic effect for glucose measurement. Pulses of light at a wavelength for which light is absorbed by glucose (e.g., 1000-1800 nm) are directed from a light guide into soft tissue of the person's body, such as a fingertip. The light pulses are typically focused to a relatively small focal region inside the body part and light from the light pulses is absorbed by glucose and converted to acoustic energy. The kinetic energy causes temperature and pressure of the absorbing tissue region to increase and generates acoustic waves, known as “photoacoustic waves”, that radiate out from the absorbing tissue. An acoustic sensor in contact with the soft tissue senses the photoacoustic waves, and the intensity of those waves is used to assay the glucose.
U.S. Pat. No. 5,941,821, which is hereby incorporated herein by reference, describes another glucometer that uses a photoacoustic effect. This device illuminates the skin surface with modulating light at a carrier wavelength at which glucose absorbs light. Glucose in the blood and interstitial fluid near the tissue surface, absorbs the light and converts the absorbed energy to kinetic energy that heats the tissue. Temperature of the tissue increases and decreases cyclically in cadence with the modulation of the light. The alternate heating and cooling of the tissue results in periodic heating of air in contact with the surface of the illuminated region, which generates sound waves in the air. A microphone measures these sound waves which are used to determine a concentration of glucose.
A third example is described by U.S. Pat. No. 6,846,288, owned by Glucon, Inc., which is hereby incorporated herein in its entirety. There, a region of interest is illuminated with at least one pulse of radiation having a wavelength at which the radiation is absorbed, to generate a change in acoustic properties of the region. Then, ultrasound is transmitted so that it is incident on the region. Changes in the incident ultrasound are measured, to determine an absorption coefficient for the radiation, which can be converted to a concentration of glucose.
Unfortunately, these approaches all suffer from a number of drawbacks. Specifically, light is scattered by body tissue, and thus even in the '904 patent where light is focused to a region inside the body, the location and size of the absorbing tissue region are not accurately known. Furthermore, the generated photoacoustic effect in soft tissue, and thus measurements of the patient's glucose levels, are not necessarily the result only of glucose concentration in the blood. Characteristics of the absorbing tissue region, such as density of blood vessels therein, can affect concentration of glucose in the absorbing region and are often not accurately known. Furthermore, calibration must account for the nature of the body part and its size, skin color, skin condition, body fat and other factors that affect light absorption, transmission and heating of soft tissue. Measurements of blood glucose levels can therefore be affected by unknown variables that substantially compromise the reliability of those measurements.
The above techniques and disclosures discuss applications on the soft tissue of the body via the skin. Other techniques have projected radiant energy through the cornea and aqueous humor of the eye to measure glucose. The concentration of glucose and oxygen in the cornea and aqueous humor reflects the concentration generally throughout the body, and so such measurements are diagnostically useful. However, several problems are associated with these techniques.
For example, in Quandt U.S. Pat. No. 3,963,019, radiant energy is projected into the eye and reflected off the iris. The reflected radiation is detected, and the optical rotation caused by passage of the reflected radiation through the cornea and aqueous humor is determined. However, this method suffers from poor sensitivity, in part because it relies on reflecting the radiant energy off the iris.
Other attempts, as shown in March U.S. Pat. No. 3,958,560 and March U.S. Pat. No. 4,014,321, project the radiant energy at a shallow angle into the cornea on one side of the eye, through the aqueous humor, and out the cornea on the opposing side of the eye. Although this test is able to achieve high accuracy, it is difficult to administer because of the shallow angle at which the radiant energy must be passed through the eye.
U.S. Pat. No. 5,560,356 describes a system that uses an implanted reflective device in the anterior chamber or cornea of the eye. The incident polarized beam of radiation is projected into through the aqueous humor and/or cornea and is refracted or optically rotated in an amount that is proportional to the concentration of glucose or other substance present. The altered beam is reflected to a receiver by an implanted reflective device and processed to determine the glucose concentration.
All of these methods, however, measure glucose in only one area of the eye at any one time, and each relies upon optical methods for transmission and return of information. It would be advantages to measure concentration of glucose or another substance without these limitations.